Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): an ambulance-based, randomised, sham-controlled, blinded, phase 3 trial

Bath, Philip M; Scutt, Polly; Anderson, Craig S; Appleton, Jason P; Berge, Evind; Cala, Lesley; Dixon, Mark; England, Timothy M; Godolphin, Peter J; Havard, Diane; Haywood, Lee; Hepburn, Trish; Krishnan, Kailash; Mair, Grant; Montgomery, Alan A; Muir, Keith; Phillips, Stephen J; Pocock, Stuart; Potter, John; Price, Chris; Randall, Marc; Robinson, Thompson G; Roffe, Christine; Rothwell, Peter M; Sandset, Else C; Sanossian, Nerses; Saver, Jeffrey L; Shone, Angela; Niroshan Siriwardena, A; Wardlaw, Joanna M; Woodhouse, Lisa J; Venables, Graham; Sprigg, Nikola; Amarenco, Pierre; Muir, Keith; Amoils, Shannon; Jarvis, Malcolm; Rothwell, Peter M; Sandercock, Peter; Asplund, Kjell; Baigent, Colin; Ankolekar, Sandeep; Howard, Harriet; Lysons, Christopher; Walker, Gemma; Gregory, Hayley; Kirby, James; Smithson, Jennifer; Keeling, Joanne; Frowd, Nadia; Gray, Robert; Dooley, Richard; Clarke, Wim; Robinson, Patricia; Kang Law, Zhe; Hodgson, Sheila; Millington, Adam; Sakka, Eleni; Buchanan, David; P...

Abstract

© 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: High blood pressure is common in acute stroke and is a predictor of poor outcome; however, large trials of lowering blood pressure have given variable results, and the management of high blood pressure in ultra-acute stroke remains unclear. We investigated whether transdermal glyceryl trinitrate (GTN; also known as nitroglycerin), a nitric oxide donor, might improve outcome when administered very early after stroke onset. Methods: We did a multicentre, paramedic-delivered, ambulance-based, prospective, randomised, sham-controlled, blinded-endpoint, phase 3 trial in adults with presumed stroke within 4 h of onset, face-arm-speech-time score of 2 or 3, and systolic blood pressure 120 mm Hg or higher. Participants were randomly assigned (1:1) to receive transdermal GTN (5 mg once daily for 4 days; the GTN group) or a similar sham dressing (the sham group) in UK-based ambulances by paramedics, with treatment continued in hospital. Paramedics were unmasked to treatment, whereas participants were masked. The primary outcome was the 7-level modified Rankin Scale (mRS; a measure of functional outcome) at 90 days, assessed by central telephone follow-up with masking to treatment. Analysis was hierarchical, first in participants with a confirmed stroke or transient ischaemic attack (cohort 1), and then in all participants who were randomly assigned (intention to treat, cohort 2) according to the statistical analysis plan. This trial is registered with ISRCTN, number ISRCTN26986053. Findings: Between Oct 22, 2015, and May 23, 2018, 516 paramedics from eight UK ambulance services recruited 1149 participants (n=568 in the GTN group, n=581 in the sham group). The median time to randomisation was 71 min (IQR 45–116). 597 (52%) patients had ischaemic stroke, 145 (13%) had intracerebral haemorrhage, 109 (9%) had transient ischaemic attack, and 297 (26%) had a non-stroke mimic at the final diagnosis of the index event. In the GTN group, participants' systolic blood pressure was lowered by 5·8 mm Hg compared with the sham group (p

Citation

Bath, P. M., Scutt, P., Anderson, C. S., Appleton, J. P., Berge, E., Cala, L., Dixon, M., England, T. M., Godolphin, P. J., Havard, D., Haywood, L., Hepburn, T., Krishnan, K., Mair, G., Montgomery, A. A., Muir, K., Phillips, S. J., Pocock, S., Potter, J., Price, C., …Mir, R. (2019). Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): an ambulance-based, randomised, sham-controlled, blinded, phase 3 trial. Lancet, 393(10175), 1009-1020. https://doi.org/10.1016/S0140-6736%2819%2930194-1

• Journal Article Type: Article
• Acceptance Date: Jan 14, 2019
• Online Publication Date: Feb 6, 2019
• Publication Date: Mar 9, 2019
• Deposit Date: Feb 8, 2019
• Publicly Available Date: Feb 11, 2019
• Journal: Lancet
• Print ISSN: 0140-6736
• Electronic ISSN: 1474-547X
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 393
• Issue: 10175
• Pages: 1009-1020
• DOI: https://doi.org/10.1016/S0140-6736%2819%2930194-1
• Public URL: https://nottingham-repository.worktribe.com/output/1529768
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0140673619301941#!
• Contract Date: Feb 8, 2019